This invention relates to extractive solution crystallization techniques for a broad class of chemical compounds, including salts of chemical compounds. More particularly, the invention relates to a process for the isolation and purification of inorganic salts or organic salts by extractive solution crystallization. In a highly preferred embodiment, the invention relates to phenyl ester salts.
Phenyl ester salts, as are known in the art, have been used in detergents and as bleach activators for fabric laundering and cleaning applications. The synthesis and purification of phenyl ester salts is described in U.S. Pat. No. 5,717,188, U.S. Pat. No. 5,650,527, and U.S. Pat. No. 5,523,434. In most cases, the phenyl ester salt to be purified is first isolated in a crude form, for example, through either evaporation of the reaction solvent, or by solid-liquid separation through filtration or centrifugation. This crude product is then purified using techniques known in the art, such as distillation or crystallization.
For the isolation and purification of solid chemical compounds, crystallization is often more appropriate than distillation. Crystallization comprises precipitating a chemical compound from a solution, followed by crystal growth. As a purification technique, crystallization has been used extensively to separate inorganic and organic chemical compounds from impurities, and thereby purifying the inorganic or organic chemical compound.
Many industrial chemical processes isolate and purify chemical compounds using crystallization techniques. Comprehensive accounts of various crystallization techniques have been discussed in several publications. (See Mullins, J. W., xe2x80x9cUllmann""s Encyclopedia of Industrial Chemistry,xe2x80x9d Volume B2, 3-1, 1988, for example). In many situations, crystallization can yield compounds of high purity in one theoretical stage with minimal energy costs. In other cases, however, crystallization may be inefficient for a variety of reasons.
One problem commonly encountered when using crystallization techniques is the co-crystallization of undesired impurities. These impurities may include, for example, unreacted starting materials or undesired byproducts produced during synthesis. In the case of phenyl ester salts, co-crystallization can lead to purity or separability problems which preclude isolation of the phenyl ester salt or which preclude its intended use in a subsequent chemical process or product. The impurities can sometimes be removed through multiple purification or recrystallization steps. However, the use of numerous purification or recrystallization steps has many disadvantages including: high capital costs, low overall yield, loss of product, poor product quality, lack of process robustness, additional steps for solvent recovery, and slower throughput. For large scale production, these problems can be particularly unacceptable.
Generally, simple fractional crystallization is used to separate and/or purify chemical compounds from crude mixtures containing the desired compound and one or more undesired impurities. Simple fractional crystallization is the sequential and separate crystallization of more than one compound from the same solution. Where simple fractional crystallization cannot be used to completely separate pure chemical compounds from mixtures, crystallization techniques such as adductive crystallization and extractive crystallization have been employed. Adductive crystallization processes have been described, for example, in U.S. Pat. Nos. 2,768,222; 2,778,864; and 2,520,716. Extractive crystallization processes have been described, for example, in U.S. Pat. Nos. 3,767,724 and 2,398,526.
Both adductive crystallization and extractive crystallization have been effectively used to (i) separate mixtures which form eutectics upon crystallization, (ii) separate pure isomers where distillation, extraction, and adsorption fail, (iii) separate compounds by shape and size rather than by chemical type, and (iv) eliminate deep refrigeration (e.g., Dale, G. H., xe2x80x9cCrystallization, Extractive and Adductive,xe2x80x9d in Encyclopedia of Chemical Processing and Design, J. J. McKetta and W. A. Cunningham, Eds., Vol. 13, p. 456, 1981).
Adductive crystallization involves adding an adductive agent to a solution containing a mixture of chemical compounds to selectively form an adduct with a desired chemical compound, which then selectively crystallizes or crystallizes out of the solution. The resulting adduct may then be separated as a solid from the mixture. The desired product is subsequently recovered by xe2x80x9cbreakingxe2x80x9d the adduct and removing the adductive agent. Disadvantages of adductive crystallization include the extra steps which are required to isolate the desired chemical compound, as well as the mechanical problems and large expense involved if this process is to be adapted for large scale production. Further, some chemical compounds, such as the detergent or bleach activators described below, may not be stable under the conditions required to remove the adductive agent from the resulting adduct of the compound.
Extractive crystallization, in contrast, involves adding an additional component, such as a solvent, to a solution containing a mixture of chemical compounds (e.g., isomers, binary pairs, or similar compounds) to lower the eutectic point of the mixture. Extractive crystallization affords enhanced recovery of the purified desired component as a solid, and may also allow the recovery of the other isomer as a purified co-product. Extractive crystallization is normally limited to separations of fairly high molecular weight compounds with relatively high freezing points (Dale, G. H., xe2x80x9cCrystallization, Extractive and Adductive,xe2x80x9d Encyclopedia of Chemical Processing and Design, J. J. McKetta and W. A. Cunningham, Eds., Vol. 13, p. 456, 1981; Dye, S. R. et al, Process Systems Engineering, 41, 1456-1470, 1995). Methods for selecting the extractive solvent for extractive crystallization have been studied (e.g., Dikshit, et al., Chem. Eng., Science, 26, 719-727, 1971). However, extractive crystallization is not readily adaptable to a wide variety of substrates or solvent systems.
Extractive crystallization has also been adapted to crystallize salts from concentrated aqueous solutions. Here, the added solvent extracts the water away from the inorganic salt phase (e.g., Weingaertner, D. L., et al., Ind. Eng. Chem. Res., 30, 490-501, 1991; Zerres, H., et al., A. I. Ch. E., 40, 676-691, 1994; Lynn Scott, A. L., et al., Ind. Eng. Chem. Res., 35, 4236-4245, 1996). This results in the crystallization and crystal growth of the salt solute, as the original aqueous phase becomes more concentrated and its saturation limit is exceeded. This mechanism is different from conventional extractive crystallizations since two liquid phases are actually present. However, both of these phases are considered to be aqueous, and not biphasic.
Another recent offshoot of extractive and adductive crystallization techniques is dissociation extractive crystallization (Lashanizadegan, A. et al., Chem. Eng. Res. and Design, Trans. Inst. Chem. Eng., 74, Part A, 1996). Here, the extractant contains a reactive agent that reacts with the desired compound in either the same phase or a separate phase. The resulting product or complex is insoluble and crystallizes out. Since the reaction is equilibrium-based, an excess of the extractant that contains the reactive agent may be used to recover the desired compound in high yields. As with adductive crystallization, however, further processing steps are required to ultimately isolate the desired product from the complex. Often, the desired product must be recovered from the complex through additional steps, such as heating or other chemical means. Similar problems as described above for adductive crystallization are encountered, which limits the utility of this technique.
Extractive crystallization using biphasic systems is described in U.S. Pat. No. 5,298,611 and U.S. Pat. No. 4,980,463. These patents are generally limited to sucralose esters, and have not been generally adapted to the purification of salts of chemical compounds or phenyl ester salts. U.S. Pat. No. 5,298,611 patent teaches using a biphasic mixture (in a ratio of 4:1 to 1:2 water to organic) for crystallization. The crystallization appears to be practiced as a xe2x80x9cdrown-outxe2x80x9d crystallization, where the second solvent is added to cause the desired compound of choice to precipitate out, rather than effecting crystallization by cooling or evaporation.
In U.S. Pat. No. 4,980,463 a sucralose pentaester is crystallized in a biphasic mixture. The crystallization of the sucralose pentaester is in the organic phase while the impurities are in the aqueous phase. The ratio of aqueous to organic appears to be between 1:1 and 1:5.
Therefore, in spite of the development of such highly complex crystallization techniques, there still exists a need in the art for a crystallization technique that produces satisfactory results in terms of ease of operation, purity of final product, and efficiency.
Such crystallization techniques are particularly needed with respect to phenyl ester salts, which are used in detergents and cleaning formulations as bleach activators. For instance, numerous solvents have been investigated for the purification of sodium 4-sulfophenyl-6-[(1-oxynonyl)-amino] hexanoate after separation from sulfolane, including acetic acid, water, methanol, isopropanol, and combinations thereof (e.g., U.S. Pat. No. 5,523,434). However, the purification of sodium 4-sulfophenyl-6-[(1-oxynonyl)-amino] hexanoate is not trivial. All the processes developed to purify sodium 4-sulfophenyl-6-[(1-oxynonyl)-amino] hexanoate have been suboptimal for reasons including poor yield, high capital costs, low rate of perhydrolysis, poor product color and lack of process robustness. Also, high capital costs are encountered in cases requiring additional crystallizations, solvent recovery, and/or special equipment for slow filtering or settling solids.
Accordingly, it would be beneficial to have a general crystallization process, (particularly for detergents and bleach activators), which avoids problems of co-crystallization, can be performed over a wide temperature range under mild conditions, and provides the desired product in high yields. The invention described below answers this need.
The invention relates to a process for the isolation and purification of salts of chemical compounds, such as phenyl ester salts, by extractive solution crystallization. Extractive solution crystallization is the process whereby a salt of an inorganic or organic chemical compound is crystallized from a solvent system comprising a first solvent and a second solvent. In this process, extraction is combined with solution crystallization. The invention is different from conventional extractive crystallization, because it employs systems with two liquid phases, one aqueous, and one organic. Additionally, the invention advantageously does not require the reaction of the desired product to form an adduct, as in adductive crystallization. Extractive solution crystallization may be particularly useful in avoiding situations where an impurity cocrystallizes with the desired product.
The first step of the process involves combining in any order: a first solvent, a second solvent, and a mixture comprising a chemical compound and at least one impurity. The solvents are selected such that the chemical compound is substantially soluble in the first solvent and substantially insoluble in the second solvent. Further, the impurity is substantially soluble in the second solvent. The second solvent is substantially immiscible in the first solvent under conditions where a chemical compound crystallizes from the first solvent. The second solvent may initially be miscible in the first solvent at the dissolution temperature of the system, and then form at least two phases during the course of the crystallization prior to the precipitation of any impurities. It is permissible for the second solvent to form a separate phase during the course of the crystallization, as long as it is present as a second phase prior to the anticipated precipitation of any impurities.
The mixture comprising a chemical compound and at least one impurity is then substantially dissolved in the solvents. The mixture may be dissolved directly in a combination of the first and second solvents. Alternatively, the mixture may be first dissolved in one solvent, followed by the addition of the second solvent, prior to the crystallization step or the precipitation of any impurities. The dissolving step can be achieved through stirring and/or heating, or other methods as will be apparent to one skilled in the art. At the end of the dissolving step, any remaining undissolved material from the above steps may be optionally removed, e.g, by filtration. The chemical compound is crystallized from the first solvent under conditions where the impurity remains substantially dissolved in the second solvent. After crystallization, the crystals are collected.
The invention describes a process that is applicable to a broad range of inorganic and organic chemical compounds as well as salts of inorganic and organic compounds. In a preferred embodiment, the invention is used as a process to purify phenyl ester salts. For clarity, the invention is described with regard to purifying phenyl ester salts. The process of the invention substantially improves the properties of the resulting purified phenyl ester salts. For salts of phenyl esters which are used as detergents or bleach activators such improvements include, but are not limited to, greater purity, larger particle size, and improved product color over other methods of purification. In addition, this invention advantageously combines into one unit operation, the previously separate steps of solid-liquid separation, extraction, drying, and re-crystallization. This reduces capital costs over multi-step processes and results in higher efficiency. In industrial process chemistry, increased throughput on a given device can be the difference between an economic process and an uneconomic process.
A further aspect of this invention is that the impurities that are dissolved in the second solvent may easily be isolated and recycled. These impurities may include unreacted starting material, or other useful side products, for instance. For large-scale production, this may be a highly desirable advantage.
In particular, the invention provides a more efficient process for the separation and purification of sodium 4-sulfophenyl-6-[(1-oxynonyl)-amino] hexanoate without requiring the pre-extraction of water insoluble impurities, or compromising on yield, stability, or purity of product. This invention alleviates problems encountered previously when crystallizing sodium 4-sulfophenyl-6-[(1-oxynonyl)-amino] hexanoate directly from water, including slow filtering and foaming during the filtration step.
Additional objects and advantages of the invention are discussed in the detailed description that follows, and will be obvious from that description, or may be learned by the practice of the invention. It is to be understood that both this summary and the following detailed description are exemplary and explanatory only and are not intended to restrict the invention.